Response of a Human Melanoma Xenograft Model to the MEK Inhibitor AZD6244 (ARRY-142886) Evaluated by Diffusion-Weighted MRI

Mounia Beloueche-Babari¹, Yann Jamin¹, Vaitha Arunan¹, Simon Walker-Samuel¹, Paul D. Smith², John C. Waterton², Jane Halliday², Martin O. Leach¹, Simon P. Robinson¹

Down-modulation of the BRAF-MEK-ERK1/2 signalling pathway is a novel strategy for targeted cancer treatment that causes tumour growth inhibition and induction of apoptosis. Diffusion-weighted MRI was used to detect pharmacodynamic biomarkers of treatment with the MEK inhibitor AZD6244. Treatment of a human melanoma xenograft model with AZD6244 caused inhibition of tumour growth that was associated with an increase in the apparent diffusion coefficient and tumour necrosis.